Oroxin A from Oroxylum indicum prevents the progression from prediabetes to diabetes in streptozotocin and high-fat diet induced mice

Abstract

BackgroundOroxylum indicum (L.) Kurz (Bignoniaceae) has been widely used for the treatment of respiratory infections and gastrointestinal disorders. Our previous study showed that an ethanol–water O. indicum seed extract (OISE), when combined with acarbose, reduced the risk of diabetes by 75% and effectively prevented the associated complications. Oroxin A, a major component of OISE, can activate PPARγ and inhibit α-glucosidase and it represents a promising candidate for diabetes intervention. PurposeThe aim of this study is to investigate the effect of oroxin A from O. indicum on the progression of prediabetes to diabetes and the underlying mechanisms in streptozotocin and high-fat-diet induced prediabetic mice. MethodsOroxin A was purified from OISE and its PPARγ transcriptional activation was determined in vitro and in vivo. The prediabetic mice were established by high-fat diet and streptozotocin, which was followed by treatment with oroxin A. The effect of oroxin A was determined by analysis of the lipid profiles, oxidative stress, hepatic function and histology. The mechanism of oroxin A was also investigated. ResultsOroxin A is a compound with low toxicity that has reduced the relative risk of progression from prediabetes to diabetes by 66.7% without inducing weight gain or hepatotoxicity. Oroxin A also improved the complications of prediabetes, such as lipid metabolism dysfunction and liver injury. Results of mechanism studies suggested that oroxin A is a partial PPARγ agonist that can activate PPARγ transcriptional activation in vitro and in vivo. Oroxin A also exhibited an inhibitory activity against α-glucosidase and an antioxidant capacity. ConclusionOroxin A prevents the progression from prediabetes to diabetes through a multi-pathway intervention mechanism.